Breakthrough in research on cancer metastasis

In an article published in this week’s edition of Cell magazine, scientists from the Hubrecht Institute, an Academy research institute, describe a major discovery in research on cancer metastasis. The scientists show that cancer cells that metastasize, can copy this behaviour to less malignant cancer cells. This discovery provides fundamental new insights into the behaviour of cancer and may offer prospects for improved diagnosis and treatment.

Cancer is caused by an accumulation of errors in the hereditary information (DNA) of cells. Some errors cause cells to ignore the signals that control growth and differentiation, leading to uncontrollable cell division. This eventually leads to the growth of a tumour in which tumour cells acquire more and more errors. Because these DNA mistakes can be different in each tumour cell (tumour heterogeneity), the behaviour of these individual tumour cells can also vary. This makes the treatment of cancer difficult: some combinations of DNA errors make certain tumour cells resistant to therapy.

Filming cancer

To better understand the behaviour of individual tumour cells, the research group of Prof. Jacco van Rheenen of the Hubrecht Institute developed special microscopy techniques (intravital microscopy) to film the behaviour of cancer cells in living organisms. The researchers gave tumour cells with different DNA errors a different colour, a ‘fluorescent label’, to let them emit light in different colours. By filming these coloured cells it became clear which cells are motile and can travel through the body to cause metastases.

Picture: 3D reconstruction of a breast tumour.Aggressive malignant cancer cells (blue) release very small vesicles containing molecules that make cells malignant. Less malignant cells (red) take up these vesicles which changes their behavior: the less malignant cells become more malignant and start metastasising (green).

Vesicles

Anoek Zomer, scientist in the research group of Prof. Jacco van Rheenen, and her colleagues used the intravital microscopy techniques to show that cancer cells with DNA errors that cause malignancy can transfer their malignant behaviour to less malignant cancer cells that do not have these DNA errors. Their movies show that malignant cancer cells release very small vesicles containing molecules that make cells malignant. By filming tumours, the scientists show that less malignant cells that take up these vesicles change their behaviour: the less malignant cells become more malignant and start metastasizing. The scientists also show that the dangerous vesicles can travel to other tumours through the blood, and that the copying of malignant behaviour can also occur over long distances.

This study shows that the behaviour of cells with certain DNA errors can be copied to cells that do not have these DNA errors. This is of great importance for follow-up studies in order to be able to better diagnose, prevent and cure cancer and metastases.

About the Hubrecht Institute

The Hubrecht Institute is a research institute of the Royal Netherlands Academy of Arts and Sciences. Presently there are 20 research groups with a total of about 200 employees. In addition to a highly interactive and international scientific environment, excellent research facilities are available for imaging and functional genomics. Moreover, several model organisms are present, including C. elegans, zebrafish and mice. The institute is situated in Utrecht at the university centre De Uithof. The Hubrecht Institute is affiliated with the University Medical Center Utrecht and has close connections with Utrecht University, e.g. in the Graduate School Cancer Genomics and Development Biology.